AN-2728CAS号： 906673-24-3分子式： C14H10BNO3分子量： 251.04描述纯度储存/保存方法别名可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)参考文献
| 产品描述 | |
| 描述 |
AN-2728 is a topical anti-inflammatory product candidate for the treatment of psoriasis and atopic dermatitis. AN-2728 inhibits PDE4 and reduces the production of TNF-alpha, a precursor of the inflammation associated with psoriasis as well as other cytokines, including IL-12 and IL-23, which are proteins believed to be involved in the inflammation process and immune responses. AN2-728 is currently in Phase 2b for psoriasis and Phase 2 for atopic dermatitis. |
| 纯度 |
98%
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| 储存/保存方法 |
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
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| 基本信息 | |
| 别名 |
AN2728；克瑞沙硼；Crisaborole
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| 可溶性/溶解性 |
DMSO ≥32 mg/mL
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| 生物活性 | |
| 靶点 |
Phosphodiesterase (PDE)
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| In vitro(体外研究) |
AN-2728 inhibits PDE4, TNF-α, IL-2, IFN-γ, IL-5 and IL-10 with IC50 values of 0.49, 0.54, 0.61, 0.83, 2.4 and 5.3 μM. AN-2728 shows the most potent activity against PDE4 catalytic domain, but it also shows inhibition against PDE1A3, PDE3Cat, and PDE7A1. AN-2728 inhibits PDE isozymes PDE1A3, PDE3Cat , PDE4Cat and PDE7A1 with IC50 values of 6.1, 6.4, 0.11 and 0.73 μM. Crystallography reveals that interaction of benzoxaboroles with the hydrophobic pocket in the PDE4 catalytic domain increase their affinity for PDE4. These benzoxaboroles strongly suppresses the secretion of cytokines associated with Ps and AD. AN-2728 is a topically administered, boron-containing, anti-inflammatory compound that inhibits PDE4 activity and thereby suppresses the release of TNFalpha, IL-12, IL-23 and other cytokines.
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| In vivo(体内研究) |
AN-2728 shows significant inhibition against the ear edema caused by phorbol ester after dosing at 1 mg/ear×2 (78% and 68%, respectively). The efficacy is comparable to that of dexamethasone, suggesting that AN-2728 has good anti-inflammatory activity as well as skin penetration. AN-2728 is reported to be well tolerated and to demonstrate significant effects on markers of efficacy, with results that were comparable to positive controls in clinical trials.
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| 参考文献 | |
| 参考文献 |
AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis.
Nazarian R,et al. Curr Opin Investig Drugs. 2009 Nov;10(11):1236-42. PMID: 分子结构图
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